Artikel
Genetic variants in the LARG gene are not associated with T2DM and related parameters in Caucasians (KORA study)
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Veröffentlicht: | 6. September 2007 |
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Gliederung
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Background: One of the characteristic features of type 2 diabetes (T2DM) is diminished insulin sensitivity. The leukemia-associated Rho guanine nucleotide exchange factor (LARG) localized on chromosome 11q23-24 is a regulator of RhoA activity, which is involved in the inhibition of insulin action. The aim of our study was to determine the variant pattern of the LARG gene in the population-based KORA Survey 4 (S4) and to investigate whether LARG variants are associated with T2DM, the metabolic syndrome (MetS) or related parameters such as insulin sensitivity in German Caucasians.
Materials and methods: We analyzed single nucleotide polymorphisms (SNPs) in the LARG gene in 55-74 year-old individuals of the population-based German Caucasian KORA study. Sequencing of the genetic variant Tyr1306Cys in 48 randomly selected individuals and genotyping of eleven additional LARG SNPs in 1653 subjects were performed. Four linkage disequilibrium (LD) blocks (r² ≥ 0.8) were established for the eleven SNPs, and one polymorphism of each block was statistically analyzed. The association with T2DM and the MetS was analyzed by logistic regression in 1,462 subjects, and HOMA-IR as a measure of insulin sensitivity was analyzed by Kruskal-Wallis test in 1,231 non diabetic subjects.
Results: The polymorphism Tyr1306Cys, which was significantly associated with insulin sensitivity in Pima Indians [Ref. 1], was monomorph in the KORA S4 population. Statistical analysis yielded no significant associations (p>0.05) between four LARG variants and T2DM, the MetS or related parameters such as insulin sensitivity.
Conclusion: Caucasian individuals of KORA S4 and Pima Indians differ in their genetic variant pattern of the LARG gene region. There is no evidence in the Caucasian KORA study that variants of the LARG gene confer susceptibility for T2DM, insulin sensitivity or the MetS.
References
- 1.
- Kovacs P, Stumvoll M, Bogardus C, Hanson RL, Baier LJ. A functional Tyr1306Cys variant in LARG is associated with increased insulin action in vivo. Diabetes. 2006;55:1497-1503.